Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001016588 | SCV001177554 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-09-03 | criteria provided, single submitter | clinical testing | The c.278_280delTTA variant (also known as p.I93del) is located in coding exon 3 of the FH gene. This variant results from an in-frame TTA deletion at nucleotide positions 278 to 280. This results in the in-frame deletion of an isoleucine at codon 93. This alteration has been observed in at least one individual who has a personal or family history that is consistent with FH-associated disease (Ambry internal data). Based on internal structural analysis, this variant is more disruptive than nearby known pathogenic variants (Ajalla Aleixo MA et al. FEBS J., 2019 May;286:1925-1940; Ambry internal data). These nucleotide positions are well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |